tbuckley/cabot-search huggingface dataset:
Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study
Authors: Aaron Waxman, Ricardo Restrepo-Jaramillo, Thenappan Thenappan, Peter Engel, Abubakr Bajwa, Ashwin Ravichandran, Jeremy Feldman, Amy Hajari Case, Rahul G. Argula, Victor Tapson, Peter Smith, Chunqin Deng, Eric Shen, Steven D. Nathan
Journal: European Respiratory Journal (2023)

Introduction The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD. Methods Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil. Assessments included 6MWD, pulmonary function testing, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events. Hospitalisations, exacerbations of underlying lung disease and death were recorded. Results At INCREASE OLE baseline, patients had a median age of 70 years and a mean 6MWD of 274.2 m; 52.1% were male. For the overall population, the mean 6MWD at week 52 was 279.1 m and the mean change from INCREASE RCT baseline was 3.5 m (22.1 m for the prior inhaled treprostinil arm and −19.5 m for the prior placebo arm); the median NT-proBNP decreased from 389 pg·mL −1 at RCT baseline to 359 pg·mL −1 at week 64; and the absolute (% predicted) mean forced vital capacity change from RCT baseline to week 64 was 51 mL (2.8%). Patients who received inhaled treprostinil versus placebo in the RCT had a 31% lower relative risk of exacerbation of underlying lung disease in the OLE (hazard ratio 0.69 (95% CI 0.49–0.97); p=0.03). Adverse events leading to drug discontinuation occurred in 54 (22.3%) patients. Conclusions These results support the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent with the results observed in the INCREASE RCT.
EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma
Authors: Domenico Alvaro, Gregory J. Gores, Joël Walicki, Cesare Hassan, Gonzalo Sapisochin, Mina Komuta, Alejandro Forner, Juan W. Valle, Andrea Laghi, Sumera I. Ilyas, Joong-Won Park, Robin K. Kelley, Maria Reig, Bruno Sangro
Journal: Journal of Hepatology (2023)
Prediction of the 3D shape of the L1 vertebral body from adjacent vertebrae
Authors: M. Sensale, T. Vendeuvre, A. Germaneau, C. Grivot, M. Rochette, E. Dall'Ara
Journal: Medical Image Analysis (2023)

The aim of treatments of vertebral fractures is the anatomical reduction to restore the physiological biomechanics of the spine and the stabilization of the fracture to allow bone healing. However, the three-dimensional shape of the fractured vertebral body before the fracture is unknown in the clinical setting. Information about the pre-fracture vertebral body shape could help surgeons to select the optimal treatment. The goal of this study was to develop and validate a method based on Singular Value Decomposition (SVD) to predict the shape of the vertebral body of L1 from the shapes of T12 and L2. The geometry of the vertebral bodies of T12, L1 and L2 vertebrae of 40 patients were extracted from CT scans available from the VerSe2020 open-access dataset. Surface triangular meshes of each vertebra were morphed onto a template mesh. The set of vectors with the node coordinates of the morphed T12, L1 and L2 were compressed with SVD and used to build a system of linear equations. This system was used to solve a minimization problem and to reconstruct the shape of L1. A leave-one-out cross-validation was performed. Moreover, the approach was tested against an independent dataset with large osteophytes. The results of the study show a good prediction of the shape of the vertebral body of L1 from the shapes of the two adjacent vertebrae (mean error equal to 0.51 ± 0.11 mm on average, Hausdorff distance equal to 2.11 ± 0.56 mm on average), compared to current CT resolution typically used in the operating room. The error was slightly higher for patients presenting large osteophytes or severe bone degeneration (mean error equal to 0.65 ± 0.10 mm, Hausdorff distance equal to 3.54 ± 1.03 mm). The accuracy of the prediction was significantly better than approximating the shape of the vertebral body of L1 by the shape of T12 or L2. This approach could be used in the future to improve the pre-planning of spine surgeries to treat vertebral fractures.
Distribution based MIL pooling filters: Experiments on a lymph node metastases dataset
Authors: Mustafa Umit Oner, Jared Marc Song Kye-Jet, Hwee Kuan Lee, Wing-Kin Sung
Journal: Medical Image Analysis (2023)

Histopathology is a crucial diagnostic tool in cancer and involves the analysis of gigapixel slides. Multiple instance learning (MIL) promises success in digital histopathology thanks to its ability to handle gigapixel slides and work with weak labels. MIL is a machine learning paradigm that learns the mapping between bags of instances and bag labels. It represents a slide as a bag of patches and uses the slide's weak label as the bag's label. This paper introduces distribution-based pooling filters that obtain a bag-level representation by estimating marginal distributions of instance features. We formally prove that the distribution-based pooling filters are more expressive than the classical point estimate-based counterparts, like 'max' and 'mean' pooling, in terms of the amount of information captured while obtaining bag-level representations. Moreover, we empirically show that models with distribution-based pooling filters perform equal to or better than those with point estimate-based pooling filters on distinct real-world MIL tasks defined on the CAMELYON16 lymph node metastases dataset. Our model with a distribution pooling filter achieves an area under the receiver operating characteristics curve value of 0.9325 (95% confidence interval: 0.8798 - 0.9743) in the tumor vs. normal slide classification task.
Muscle sympathetic nerve activity and adaptive servo-ventilation: questions remain
Authors: Dany Jaffuel, Jean Pierre Mallet, François Roubille, Arnaud Bourdin
Journal: European Respiratory Journal (2023)

Sudden cardiac death presumably due to cardiac arrhythmias is one of the hypotheses to explain the observed higher cardiovascular mortality in the adaptive servo-ventilation (ASV) group of the SERVE-HF study [1, 2]. In this regard, we congratulate Tamisier et al . [3] for their efforts to clarify the effect of ASV on muscle sympathetic nerve activity (MSNA) in patients with central sleep apnoea (CSA) and heart failure with reduced left ventricular ejection fraction (HFrEF). Analysing data from an SERVE-HF ancillary study, they concluded that: 1) suppression of CSA with ASV did not seem to have a significant effect on chronic HFrEF-related sympathetic activation; and 2) simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality. In our opinion, these conclusions might be different if some confounding factors were considered. Stratified analyses of ongoing trials will need to take adaptive servo-ventilation (ASV) efficacy into account before concluding on ASV impact on outcome measures https://bit.ly/3GpHAD4
Preventable mortality in the Russian Federation: a retrospective, regional level study
Authors: Zlatko Nikoloski, Vladimir M. Shkolnikov, Elias Mossialos
Journal: The Lancet Regional Health - Europe (2023)

Background Avoidable mortality, including both treatable and preventable deaths, is frequently used as an indicator of health system performance.Whilst the term treatable mortality refers to deaths that might be averted by medical interventions, preventable mortality generally reflects the impact of system-wide health policies.The concept of preventable mortality has not been evaluated extensively in the Russian Federation, particularly at the regional or sub-national (oblast) level. MethodsWe calculated total preventable mortality as well as individual rates for males and females in each oblast using data from the Russian Fertility and Mortality Database (RusFMD) and computed the contributions of specific preventable causes of death to the overall rates.We also evaluated the relationship between preventable mortality and its main correlates during the years 2014-2018 using panel fixed effects modelling with variables that reflected both, behavioural risk factors and access to health care.Findings Overall preventable mortality in the Russian Federation has been on a downward trend.Whilst 548 preventable deaths per 100,000 person-years were reported in the year 2000, only 301 per 100,000 person-years were reported in 2018.Whilst mortality due to cancer, cardiovascular, and alcohol-related diseases has declined (albeit unevenly) amongst both males and females, deaths resulting from complications of diabetes and human immunodeficiency virus infection have increased.Our findings also revealed significant heterogeneity in preventable mortality at the oblast level.For example, in 2018, deaths due to preventable causes were concentrated primarily in Siberia and the Far East.Smoking and the availability of nurses were identified as significant correlates of preventable mortality at the oblast level.Interpretations Efforts designed to strengthen the current health care system, notably those serving the rural and less densely populated oblasts, might reduce the rate of preventable mortality in Russia.These efforts might be coupled with an ongoing focus on programs designed to reduce smoking.
The lymph node yield in the initial lateral neck dissection predicts recurrence in the lateral neck of papillary thyroid carcinoma: a revision surgery cohort study
Authors: Shi-Tong Yu, Junna Ge, Zhigang Wei, Baihui Sun, Zizheng Xiao, Tingting Li, Zhicheng Zhang, Weisheng Chen, Shang-Tong Lei
Journal: International Journal of Surgery (2023)

Background: This study aimed to evaluate the relationship between lateral lymph node yield (LLNY) and the ratio of lateral positive lymph nodes to lymph node yield (LPLR) from initial lateral neck dissection (LND) in patients with papillary thyroid carcinoma (PTC), as well as the risk of recurrence in patients undergoing LND reoperations. Methods: This retrospective cohort study enrolled patients with PTC who underwent revision LND between 1 January 2012, and 31 December 2021. The initial and revised clinical data were retrieved. Patient demographics, clinicopathological features, clinical records, and follow-up information were also reviewed. LLNY and LPLR were determined during the initial LND. Results: In total, 156 patients with PTC were included in this study, with a median follow-up of 36.5 months; 107 had recurrent lateral neck disease. The optimal LLNY and LPLR cutoff values for recurrent/persistent disease were 24.5 and 32.74%, respectively. The high-risk group (LLNY&lt;25) had the lowest recurrence-free survival rate compared with to moderate-risk group (LLNY≥25, LPLR≥32.74%) and low-risk group (LLNY≥25, LPLR&lt;32.74%) ( P &lt;0.001). The moderate-risk group had lower recurrence-free survival than the low-risk group. Multivariate analysis revealed that an LLNY less than 25 in the initial LND was an independent risk factor for recurrence/persistence of lateral neck ( P &lt;0.001). Conclusions: This study identified that LLNY and LPLR were associated with recurrence/persistence in PTC patients at the time of revision surgery was performed.
Eftrenonacog Alfa: A Review in Haemophilia B
Authors: Yvette N. Lamb, Sheridan M. Hoy
Journal: Drugs (2023)

Eftrenonacog alfa (Alprolix®) is an extended half-life recombinant factor IX (rFIX)-Fc fusion protein (hereafter referred to as rFIXFc). Administered as an intravenous bolus, it is approved for prophylactic use and the treatment of bleeding in patients with haemophilia B in various countries worldwide, including those of the EU, as well as the USA. In multinational, phase III trials, rFIXFc was effective for the prophylaxis, perioperative management or on-demand treatment of bleeding in male patients with severe haemophilia B regardless of age and irrespective of whether or not they had been previously treated with FIX replacement products. Prophylactic efficacy was maintained over the longer term (up to 5 years) in previously treated patients. rFIXFc effectiveness in the real-world setting is supported by results of prospective studies, as well as the outcomes of several retrospective trials. rFIXFc was well tolerated in clinical trials in previously treated and untreated children, adolescents and/or adults with severe haemophilia B. Thus, rFIXFc continues to represent a useful treatment option among the haemophilia B patient population. Haemophilia B is a rare inherited bleeding disorder caused by a deficiency in coagulation factor IX (FIX). Its management involves rectifying the deficiency in FIX by administering an FIX replacement product, thereby increasing FIX activity and reducing bleeding. FIX replacement therapy can be administered at the time of bleeding (i.e. as on-demand treatment) or prophylactically (as scheduled injections), as well as before surgery. Eftrenonacog alfa (also known as rFIXFc; Alprolix®) is a replacement FIX therapy comprising FIX linked to a region of human immunoglobulin G to prolong the half-life of the product. It has been approved for the prevention and treatment of bleeding in patients with haemophilia B in various countries worldwide. Designed to require less frequent injections, rFIXFc was effective and well tolerated when used to prevent or treat bleeding, including before surgery, in individuals with haemophilia B regardless of age or whether they have been treated previously with an FIX replacement product. Thus, rFIXFc continues to represent a useful treatment option for individuals with haemophilia B.
Genetics of myocardial interstitial fibrosis in the human heart and association with disease
Authors: Victor Nauffal, Paolo Di Achille, Marcus D. R. Klarqvist, Jonathan W. Cunningham, Matthew C. Hill, James P. Pirruccello, Lu-Chen Weng, Valerie N. Morrill, Seung Hoan Choi, Shaan Khurshid, Samuel F. Friedman, Mahan Nekoui, Carolina Roselli, Kenney Ng, Anthony A. Philippakis, Puneet Batra, Patrick T. Ellinor, Steven A. Lubitz
Journal: Nature Genetics (2023)
Postoperative Adjuvant Anastrozole for 10 or 5 Years in Patients With Hormone Receptor–Positive Breast Cancer: AERAS, a Randomized Multicenter Open-Label Phase III Trial
Authors: Takuji Iwase, Shigehira Saji, Kotaro Iijima, Kenji Higaki, Shoichiro Ohtani, Yasuyuki Sato, Yasuo Hozumi, Yoshie Hasegawa, Yasuhiro Yanagita, Hiroyuki Takei, Maki Tanaka, Hideji Masuoka, Masahiko Tanabe, Chiyomi Egawa, Yoshifumi Komoike, Toshitaka Nakamura, Hiroshi Ohtsu, Hirofumi Mukai
Journal: Journal of Clinical Oncology (2023)

Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on disease-free survival (DFS).This prospective, randomized, multicenter open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients who were disease-free after treatment with either 5 years of anastrozole alone or 2-3 years of tamoxifen followed by 2-3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole for an additional 5 years or stop anastrozole. The primary end point was DFS, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with University Hospital Medical Information Network, Japan (UMIN) clinical trials registry (UMIN000000818).We enrolled 1,697 patients from 117 facilities between November 2007 and November 2012. Follow-up information was available for 1,593 patients (n = 787 in the continue group, n = 806 in the stop group), who were defined as the full analysis set, including 144 patients previously treated with tamoxifen and 259 patients who underwent breast-conserving surgery without irradiation. The 5-year DFS rates were 91% (95% CI, 89 to 93) in the continue group and 86% (95% CI, 83 to 88) in the stop group (hazard ratio, 0.61; 95% CI, 0.46 to 0.82; P < .0010). Notably, extended anastrozole treatment reduced the incidence of local recurrence (continue group, n = 10; stop group, n = 27) and second primary cancers (continue group, n = 27; stop group, n = 52). There was no significant difference in overall or distant DFS. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than those in the stop group, but the incidence of grade ≥3 adverse events was <1% in both groups.Continuing adjuvant anastrozole for an additional 5 years after 5 years of initial treatment with anastrozole or tamoxifen followed by anastrozole was well tolerated and improved DFS. Although no difference in overall survival was observed as in other trials, extended anastrozole therapy could be one treatment choice in postmenopausal patients with hormone receptor-positive breast cancer.
Prevention of Hepatocellular Carcinoma (HCC). White Paper of the Texas Collaborative Center for Hepatocellular Cancer (TeCH) Multi-stakeholder Conference
Authors: Hashem B El-Serag, John W Ward, Sumeet K Asrani, Amit G Singal, Nicole Rich, Aaron P Thrift, Salil Deshpande, Barbara J Turner, Ahmed O Kaseb, Ariel C Harrison, Brett E Fortune, Fasiha Kanwal
Journal: Clinical Gastroenterology and Hepatology (2023)
Virtual high-resolution MR angiography from non-angiographic multi-contrast MRIs: synthetic vascular model populations for in-silico trials
Authors: Yan Xia, Nishant Ravikumar, Toni Lassila, Alejandro F. Frangi
Journal: Medical Image Analysis (2023)

Despite success on multi-contrast MR image synthesis, generating specific modalities remains challenging. Those include Magnetic Resonance Angiography (MRA) that highlights details of vascular anatomy using specialised imaging sequences for emphasising inflow effect. This work proposes an end-to-end generative adversarial network that can synthesise anatomically plausible, high-resolution 3D MRA images using commonly acquired multi-contrast MR images (e.g. T1/T2/PD-weighted MR images) for the same subject whilst preserving the continuity of vascular anatomy. A reliable technique for MRA synthesis would unleash the research potential of very few population databases with imaging modalities (such as MRA) that enable quantitative characterisation of whole-brain vasculature. Our work is motivated by the need to generate digital twins and virtual patients of cerebrovascular anatomy for in-silico studies and/or in-silico trials. We propose a dedicated generator and discriminator that leverage the shared and complementary features of multi-source images. We design a composite loss function for emphasising vascular properties by minimising the statistical difference between the feature representations of the target images and the synthesised outputs in both 3D volumetric and 2D projection domains. Experimental results show that the proposed method can synthesise high-quality MRA images and outperform the state-of-the-art generative models both qualitatively and quantitatively. The importance assessment reveals that T2 and PD-weighted images are better predictors of MRA images than T1; and PD-weighted images contribute to better visibility of small vessel branches towards the peripheral regions. In addition, the proposed approach can generalise to unseen data acquired at different imaging centres with different scanners, whilst synthesising MRAs and vascular geometries that maintain vessel continuity. The results show the potential for use of the proposed approach to generating digital twin cohorts of cerebrovascular anatomy at scale from structural MR images typically acquired in population imaging initiatives.
Amino acids downregulate SIRT4 to detoxify ammonia through the urea cycle
Authors: Song-Hua Hu, Yu-Yang Feng, Yuan-Xin Yang, Hui-Da Ma, Shu-Xian Zhou, Ya-Nan Qiao, Kai-Hui Zhang, Lei Zhang, Lin Huang, Yi-Yuan Yuan, Yan Lin, Xin-Yan Zhang, Yao Li, Hai-Tao Li, Jian-Yuan Zhao, Wei Xu, Shi-Min Zhao
Journal: Nature Metabolism (2023)
Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression
Authors: Sujata Jana, Sandipan Brahma, Sonali Arora, Cynthia L. Wladyka, Patrick Hoang, Steven Blinka, Rowan Hough, Jessie L. Horn, Yuzhen Liu, Li-Jie Wang, Philippe Depeille, Eric Smith, Robert B. Montgomery, John K. Lee, Michael C. Haffner, Funda Vakar-Lopez, Petros Grivas, Jonathan L. Wright, Hung-Ming Lam, Peter C. Black, Jeroen P. Roose, Alexey G. Ryazanov, Arvind R. Subramaniam, Steven Henikoff, Andrew C. Hsieh
Journal: Cancer Cell (2023)

We uncover a tumor-suppressive process in urothelium called transcriptional-translational conflict caused by deregulation of the central chromatin remodeling component ARID1A. Loss of Arid1a triggers an increase in a nexus of pro-proliferation transcripts, but a simultaneous inhibition of the eukaryotic elongation factor 2 (eEF2), which results in tumor suppression. Resolution of this conflict through enhancing translation elongation speed enables the efficient and precise synthesis of a network of poised mRNAs resulting in uncontrolled proliferation, clonogenic growth, and bladder cancer progression. We observe a similar phenomenon in patients with ARID1A-low tumors, which also exhibit increased translation elongation activity through eEF2. These findings have important clinical implications because ARID1A-deficient, but not ARID1A-proficient, tumors are sensitive to pharmacologic inhibition of protein synthesis. These discoveries reveal an oncogenic stress created by transcriptional-translational conflict and provide a unified gene expression model that unveils the importance of the crosstalk between transcription and translation in promoting cancer.
The path to tuberculosis elimination: a renewed vision
Authors: Giovanni Battista Migliori, David Dowdy, Justin T. Denholm, Lia D'Ambrosio, Rosella Centis
Journal: European Respiratory Journal (2023)

Tuberculosis (TB) elimination and pre-elimination, with thresholds of 1 and 10 incident cases per million population, respectively, were considered achievable for low TB incidence countries in the 1990s, when they were conceived. However, it has since become clear that, even in low TB incidence settings with effective programmes and sufficient resources, achieving pre-elimination in the next decade will require a dramatic acceleration of efforts. In this review, we describe the history of the TB elimination concept and existing country experiences, as well as the interventions available to accelerate the progress towards this threshold. We then propose a framework for near-term progress towards the more aspirational goal of TB pre-elimination. This framework consists of five stages (high incidence, moderate incidence, low incidence, nearing pre-elimination and pre-elimination) that are benchmarked to specific levels of TB incidence in each country. Using this framework, countries can set 5-year targets of achieving certain reductions in TB incidence and/or reaching the next stage, through the use of strategies tailored to both local epidemiology and available organisation and infrastructure. TB elimination remains as an aspirational goal in all stages, but certain activities can be prioritised in the short term to make more rapid progress, ensure local-level buy-in and increase accountability. As TB pre-elimination is approached, certain ethical and social concerns are likely to rise in importance; these concerns are also discussed. Our aim in setting this framework is to guide clinicians, public health experts and decision makers in taking actionable next steps in the trajectory towards TB pre-elimination and elimination.